Correlation of High-Grade Osteosarcoma Response to Chemotherapy with Enhanced Tissue Immunological Response: Analysis of CD95R, IFN-γ, Catalase, Hsp70, and VEGF.

High-grade osteosarcoma, a primary malignant bone tumour, is experiencing a global increase in reported incidence with varied prevalence. Despite advances in management, which include surgery and neoadjuvant chemotherapy often an unsatisfactory outcome is found due to poor or heterogeneous response to chemotherapy. Our study delved into chemotherapy responses in osteosarcoma patients and associated molecular expressions, focusing on CD95 receptor (CD95R), interferon (IFN)-γ, catalase, heat-shock protein (Hsp)70, and vascular endothelial growth factor (VEGF). Employing immunohistochemistry and Huvos grading of post-chemo specimens, we analysed formalin-fixed paraffin-embedded (FFPE) osteosarcoma tissue of resected post-chemotherapy specimens from Dr. Soetomo General Academic Hospital in Surabaya, Indonesia (DSGAH), spanning from 2016 to 2020. Results revealed varied responses (poor 40.38%, moderate 48.08%, good 11.54%) and distinct patterns in CD95R, IFN-γ, catalase, Hsp70, and VEGF expression. Significant differences among response groups were observed in CD95R and IFN-γ expression in tumour-infiltrating lymphocytes. The trend of diminishing CD95R expression from poor to good responses, accompanied by an increase in IFN-γ, implied a reduction in the count of viable osteosarcoma cells with the progression of Huvos grading. Catalase expression in osteosarcoma cells was consistently elevated in the poor response group, while Hsp70 expression was highest. VEGF expression in macrophages was significantly higher in the good response group. In conclusion, this study enhances our understanding of immune-chemotherapy interactions in osteosarcoma and identifies potential biomarkers for targeted interventions.

Establishment, characterization, and genetic profiling of patient-derived osteosarcoma cells from a patient with retinoblastoma.

Osteosarcoma is the most common malignant bone cancer in pediatric patients. Patients who respond poorly to chemotherapy experience worse clinical outcomes with a high mortality rate. The major challenge is the lack of effective drugs for these patients. To introduce new drugs for clinical approval, preclinical studies based on in vitro models must demonstrate the potency of the tested drugs, enabling the drugs to enter phase 1 clinical trials. Patient-derived cell culture is a promising testing platform for in vitro studies, as they more accurately recapitulate cancer states and genetic profiles compared to cell lines. In the present study, we established patient-derived osteosarcoma cells (PDC) from a patient who had previously been diagnosed with retinoblastoma. We identified a new variant of a germline mutation in the RB1 gene in the tissue of the patient. The biological effects of this PDC were studied to observe whether the cryopreserved PDC retained a feature of fresh PDC. The cryopreserved PDC preserved the key biological effects, including cell growth, invasive capability, migration, and mineralization, that define the conserved phenotypes compared to fresh PDC. From whole genome sequencing analysis of osteosarcoma tissue and patient-derived cells, we found that cryopreserved PDC was a minor population in the origin tissue and was selectively grown under the culture conditions. The cryopreserved PDC has a high resistance to conventional chemotherapy. This study demonstrated that the established cryopreserved PDC has the aggressive characteristics of osteosarcoma, in particular the chemoresistance phenotype that might be used for further investigation in the chemoresistant mechanism of osteosarcoma. In conclusion, the approach we applied for primary cell culture might be a promising method to generate in vitro models for functional testing of osteosarcoma.

Transpedicular Contrast-enhanced CT-guided biopsy of the body and dens of the axis avoiding the trans-oral approach: Technical report and literature review.

This technical report illustrates the technique to perform computed tomography (CT)-guided bone biopsies in the body and dens of the axis (C2 vertebra) through a posterior transpedicular approach with the use of preoperative contrast-enhanced scans to highlight the course of the vertebral artery. The technique is presented through two exemplification cases: a pediatric patient with osteoblastoma and secondary aneurysmal bone cyst and one adult patient with melanoma metastasis. This case highlights the potential of the CT-guided posterolateral/transpedicular approach for performing safe and effective biopsies in the body and dens of C2, even in pediatric patients.

Telangiectatic osteosarcoma in four dogs: Cytologic, histopathologic, cytochemical, and immunohistochemical findings.

Telangiectatic osteosarcoma is a rare variant of osteosarcoma histologically and clinically similar to hemangiosarcoma (HSA). This case series describes the imaging and cytologic features of four histologically confirmed telangiectatic osteosarcomas, including the use of cytochemical stains. Alkaline phosphatase (ALP) was applied to Wright-Giemsa-stained cytology slides, and Factor VIII immunohistochemistry was evaluated. Cytologic characteristics included atypical mesenchymal cells with evidence of acute and chronic hemorrhage. Telangiectatic osteosarcoma cases had positive ALP cytochemical staining, while control HSA cases were negative. Factor VIII immunohistochemistry was negative in telangiectatic osteosarcoma and positive in HSA. Cytologic diagnosis of telangiectatic osteosarcoma with positive ALP cytochemical staining can help differentiate this neoplasm from HSA.

X-rays radiomics-based machine learning classification of atypical cartilaginous tumour and high-grade chondrosarcoma of long bones.

BACKGROUND: Atypical cartilaginous tumour (ACT) and high-grade chondrosarcoma (CS) of long bones are respectively managed with active surveillance or curettage and wide resection. Our aim was to determine diagnostic performance of X-rays radiomics-based machine learning for classification of ACT and high-grade CS of long bones. METHODS: This retrospective, IRB-approved study included 150 patients with surgically treated and histology-proven lesions at two tertiary bone sarcoma centres. At centre 1, the dataset was split into training (n = 71 ACT, n = 24 high-grade CS) and internal test (n = 19 ACT, n = 6 high-grade CS) cohorts, respectively, based on the date of surgery. At centre 2, the dataset constituted the external test cohort (n = 12 ACT, n = 18 high-grade CS). Manual segmentation was performed on frontal view X-rays, using MRI or CT for preliminary identification of lesion margins. After image pre-processing, radiomic features were extracted. Dimensionality reduction included stability, coefficient of variation, and mutual information analyses. In the training cohort, after class balancing, a machine learning classifier (Support Vector Machine) was automatically tuned using nested 10-fold cross-validation. Then, it was tested on both the test cohorts and compared to two musculoskeletal radiologists' performance using McNemar's test. FINDINGS: Five radiomic features (3 morphology, 2 texture) passed dimensionality reduction. After tuning on the training cohort (AUC = 0.75), the classifier had 80%, 83%, 79% and 80%, 89%, 67% accuracy, sensitivity, and specificity in the internal (temporally independent) and external (geographically independent) test cohorts, respectively, with no difference compared to the radiologists (p ≥ 0.617). INTERPRETATION: X-rays radiomics-based machine learning accurately differentiates between ACT and high-grade CS of long bones. FUNDING: AIRC Investigator Grant.

Expansive Central Ossifying Fibroma of the Right Mandible.

This case report discusses a 28-year-old patient who presented with a large expansile lesion of the right mandible. A maxillofacial CT showed a 6.7 x 9.1 x 7.6 cm right mandibular cystic mass containing an internal matrix of ground glass bone, representing a huge odontogenic keratocyte. Upon biopsy of the lesion, the specimen consisted of non-decalcified irregular fragments of cemento-osseous material, embedded in a minimally hemorrhagic, cellular fibrous tissue stroma, suggestive of central ossifying fibroma. This case presents an ossifying fibroma that far exceeds the average size of these masses, which typically range from 1.0 to 2.5 cm at its greatest dimension. The immense size of the lesion seen in this case is rarely encountered. This case also helps to emphasize the importance of timely diagnosis and complete resection of the lesion to prevent mass recurrence and possible malignant transformation.

Bone metastases from chondroblastoma: a rare pattern of metastatic disease in an adult.

Chondroblastoma is a rare benign tumor, typically presenting in the first two decades. Systemic metastases in chondroblastoma are extremely rare and it is the rarity of these metastases which lead the World Health Organisation to re-classify this lesion from "intermediate" to "benign" in its updated classification of bone tumors in 2020. We present an unusual case of a 55 year-old male patient who presented with multiple FDG-avid bone lesions on a background of conventional chondroblastoma of the rib excised at another institution 11-years previously. Two of these lesions were also histologically-proven as conventional chondroblastoma at biopsy. This case highlights that, although rare, metastases can be seen in patients with chondroblastoma. To our knowledge, this is the only case with an unusual pattern of metastases limited to bone.

Intratemporal facial nerve neurofibroma causing facial paralysis in an infant: Case report and review of the literature.

This article describes the first recorded case of intratemporal neurofibroma in an infant. A literature review of all other existing cases of intratemporal neurofibroma is performed, finding that the majority of cases involve multiple segments and can be found in the mastoid segment most often. Most common symptoms described included facial paralysis, otalgia, and conductive hearing loss, respectively.

Solitary Osteochondroma at Unusual Sites: A Case Report and Literature Review.

Osteochondromas (OCs) are bone lesions composed of cartilaginous and medullary bone capped with hyaline cartilage. OCs result from the separation of epiphyseal growth plate cartilage, pushing through the periosteal bone cuff. They commonly appear as pedunculated or sessile masses in the metaphysis of long bones and are the most common benign bone tumors. While rare in the scapula, OCs can occur there. Symptoms may arise from fractures, osseous abnormalities, or potential malignant transformation, especially in the presence of hereditary multiple exostoses (HME). The estimated rate of malignant transformation in solitary lesions is 1%, whereas in hereditary multiple OCs, it can reach up to 3-5%. We report a case of a 10-year-old female who presented with a gradually progressive swelling on the back of her right scapula. This progressive growth has been observed over the course of the past two years accompanied by mild pain. The pain was intermittent and did not affect her daily activities. On examination, a hard, tender, non-mobile swelling of approximately 2 × 2 cm was found over the right scapula. The patient had a normal range of motion in the shoulder and scapulothoracic regions. In conclusion, since solitary scapular OCs are extremely rare, they are quite common when associated with HME. This study aimed to increase awareness of the unusual site of OCs. Furthermore, we have included a full account of the surgical therapy we administered to this patient in order to assist future surgeons who may come across similar conditions.

Does the use of polymethyl-methacrylate cement after intralesional curettage of giant cell tumors of appendicular bone guarantee reduced local recurrence rates? A retrospective analysis.

PURPOSE: Polymethyl-methacrylate cement (PMMA) is often used as bone defect reconstruction material after surgical removal of giant cell tumors. The purpose of this study was to investigate if the application of PMMA improves the local recurrence rates for giant cell tumors (GCT) of appendicular bone treated with intralesional curettage. METHODS: A retrospective analysis of all appendicular GTCs treated at two major Danish sarcoma centres between the 1st of January 1998 and December 31st 2013; minimum follow-up of 3.0 years (median: 8.9; 1.3-18.7 years). Kaplan-Meier survival model, log-rank and multivariate Cox regression were used to calculate and compare local recurrence rates. p-values <0.05 were considered statistically significant. RESULTS: 102 patients (M59/F43), median age 31Y (11-84) were included in this study. The overall 3-years local recurrence-rate was 19.9% (95%CI: 11.9-27.9%); 91% had occurred within 3 years. In patients treated with intralesional curettage (n = 64), the 3-years recurrence-rate was 30.6% (95%CI: 18.8-42.4%), compared to 2.6% (95%CI: 0.0-7.8%) in patients treated with wide resection or amputation (n = 38), p < .001. The 3-years recurrence-rate for patients treated with intralesional curettage and reconstruction using PMMA was 29.0% (95%CI: 12.6-45.4%) and without PMMA: 31.8% (95%CI: 15.2-48.4%), p = .83. CONCLUSION: We found that the use of PMMA for bone defect reconstruction after intralesional curettage of GTCs in the appendicular skeleton did not ensure a reduced risk of local recurrence.

Brown Tumour in Chronic Kidney Disease: Revisiting an Old Disease with a New Perspective.

Osteitis fibrosa cystica (OFC) and Brown Tumours are two related but distinct types of bone lesions that result from the overactivity of osteoclasts and are most often associated with chronic kidney disease (CKD). Despite their potential consequences, these conditions are poorly understood because of their rare prevalence and variability in their clinical manifestation. Canonically, OFC and Brown Tumours are caused by secondary hyperparathyroidism in CKD. Recent literature showed that multiple factors, such as hyperactivation of the renin-angiotensin-aldosterone system and chronic inflammation, may also contribute to the occurrence of these diseases through osteoclast activation. Moreover, hotspot KRAS mutations were identified in these lesions, placing them in the spectrum of RAS-MAPK-driven neoplasms, which were until recently thought to be reactive lesions. Some risk factors contributed to the occurrence of OFC and Brown Tumours, such as age, gender, comorbidities, and certain medications. The diagnosis of OFC and Brown Tumours includes clinical symptoms involving chronic bone pain and laboratory findings of hyperparathyroidism. In radiological imaging, the X-ray and Computed tomography (CT) scan could show lytic or multi-lobular cystic alterations. Histologically, both lesions are characterized by clustered osteoclasts in a fibrotic hemorrhagic background. Based on the latest understanding of the mechanism of OFC, this review elaborates on the manifestation, diagnosis, and available therapies that can be leveraged to prevent the occurrence of OFC and Brown Tumours.

Unraveling the enigma of Adamkiewicz: exploring the prevalence, anatomical variability, and clinical impact in spinal embolization procedures for bone metastases.

BACKGROUND: The artery of Adamkiewicz (AKA) is vital for spinal cord blood supply. Its role in embolization procedures for bone metastases can cause serious complications. We explored its prevalence, anatomical variation, and effect on spinal embolization using N-butyl cyanoacrylate (NBCA) in patients with bone metastases. PURPOSE: To understand the impact and variability of AKA in spinal embolizations in cases of bone metastases to reduce complications and improve patient outcomes. MATERIAL AND METHODS: We examined data from 454 patients who underwent spinal embolization with NBCA between 2009 and 2018. The presence, anastomoses, and tumor features of AKA were assessed via pre-procedure imaging and angiography. Complications were classified per the CIRSE Classification System. RESULTS: AKA was found in 22.8% of patients, predominantly left-sided and originating from T8 to L1. Direct and indirect anastomoses were present in 66.6% and 33.4% of patients, respectively. Extra-compartmental invasion was linked with direct anastomosis (P = 0.004). High-grade complications were rare but included one instance of bilateral lower limb paralysis. Partial embolization was necessary in 22.8% of cases due to AKA. CONCLUSION: The study underscores the need for rigorous preoperative evaluation of AKA origin and anastomoses in patients undergoing spinal embolization for bone metastases. Given the significant presence of AKA and related anastomoses, especially with renal extra-compartmental tumors, caution is advised to reduce complications and optimize patient outcomes. Further research is required for best practice guidelines involving bone metastases and AKA.

Percutaneous CT-Guided Bone Biopsies: Indications, Feasibility and Diagnostic Yield in the Different Skeletal Sites-From the Skull to the Toe.

CT-guided bone biopsies are currently the diagnostic tool of choice for histopathological (and microbiological) diagnoses of skeletal lesions. Several research works have well-demonstrated their safety and feasibility in almost all skeletal regions. This comprehensive review article aims at summarizing the general concepts in regard to bone biopsy procedures, current clinical indications, the feasibility and the diagnostic yield in different skeletal sites, particularly in the most delicate and difficult-to-reach ones. The choice of the correct imaging guidance and factors affecting the diagnostic rate, as well as possible complications, will also be discussed. Since the diagnostic yield, technical difficulties, and complications risk of a CT-guided bone biopsy significantly vary depending on the different skeletal sites, subdivided analyses of different anatomical sites are provided. The information included in the current review article may be useful for clinicians assisting patients with possible bone neoplasms, as well as radiologists involved in the imaging diagnoses of skeletal lesions and/or in performing bone biopsies.

Osteosarcoma of the Proximal Fibula: A Case Report and Review of the Literature.

Osteosarcoma is the most common primary malignant bone tumor, especially in younger patients. Diagnosis is based on the combined evaluation of radiological, clinical, and pathological examinations. It is usually located in the distal femur, proximal tibia, and proximal humerus. The fibula is a rare localization for osteosarcoma. Surgery in this region is challenging due to the complex anatomic structures around the knee. Especially the peroneal nerve, lateral collateral ligament (LCL), and popliteal vessel branches are of critical importance. However, additional structures such as the arcuate ligament, biceps femoris, and iliotibial band play an essential role in the stabilization of the knee. Thus, these structures must be protected as much as possible. This case report aims to present the diagnosis and treatment process of conventional osteosarcoma in the proximal fibula, which was located close to the peroneal nerve and required LCL reconstruction after the resection.

Well-differentiated chrondrosarcoma in a cynomolgus macaque (Macaca fascicularis).

A cynomolgus macaque presented with an osteolytic lesion of the left femur. Histopathology was consistent with well-differentiated chondrosarcoma. No metastasis was found in chest radiographs out to 12 months. This case suggests survival out to 1 year without metastasis following amputation may be possible in NHPs with this condition.

3D-printed hemipelvic prosthesis combined with a dual mobility bearing in patients with primary malignant neoplasm involving the acetabulum: clinical outcomes and finite element analysis.

BACKGROUND: Limb salvage reconstruction for pelvic tumors, especially periacetabular tumors, is challenging. We combined the use of dual mobility bearing and 3D-printed hemipelvic prosthesis to improve function and reduce the probability of complications after hemi-pelvic resection in patients with primary acetabular malignancy. The purpose of this study was to evaluate the efficacy and safety of this combination. METHODS: Between October 2011 and May 2021, 11 patients with malignancies involving the acetabulum received hemipelvic replacement with a 3D-printed prosthesis and dual mobility bearing. Follow-up of postoperative survival, complications, and Musculoskeletal Tumor Society 93 (MSTS-93) lower limb functional scores were carried out. A finite element model of the postoperative pelvis was developed and input into the finite element analysis software. The Von Mises equivalent stress formula was used to analyze the stress distribution of each part of the pelvis under one gait cycle and the stress distribution at different angles of the hip joint. RESULTS: By the last follow-up, 9 of the 11 patients (81.8%) were still alive, and 2 patients had local tumor recurrence. The complications including 1 deep infection and 1 dislocation of the artificial joint. Excluding 1 amputation patient, the average score of the remaining 8 patients at the last follow-up was 21.4/30 (71.3%) on the MSTS-93. In the reconstructed pelvis, stress distributions were concentrated on the junction between hemipelvic prosthesis and screw and iliac bone on the resected side, and between femoral prosthesis stem and femoral bulb, while the stress of polyethylene lining was small. Before impact, the polyethylene lining will rotate at a small angle, about 3°. The inner stress of polyethylene liner is greater than the outer stress in all conditions. The polyethylene liner has no tendency to slide out. CONCLUSION: Pelvic tumor resection and reconstruction using 3D-printed hemipelvic prosthesis combined with dual mobility bearing was an effective treatment for pelvic tumors. Our patients achieved good early postoperative efficacy and functional recovery. The dual mobility bearing is beneficial to prevent dislocation, and the mechanical distribution and wear of the prosthesis are acceptable.

Histone Deacetylase Inhibitors as a Therapeutic Strategy to Eliminate Neoplastic "Stromal" Cells from Giant Cell Tumors of Bone.

The neoplastic "stromal" cells in giant cell tumor of bone (GCTB) harbor a mutation in the H3F3A gene, which causes alterations in the epigenome. Current systemic targeted therapies, such as denosumab, do not affect the neoplastic cells, resulting in relapse upon treatment discontinuation. Therefore, this study examined whether targeting the epigenome could eliminate the neoplastic cells from GCTB. We established four novel cell lines of neoplastic "stromal" cells that expressed the H3F3A p.G34W mutation. These cell lines were used to perform an epigenetics compound screen (n = 128), which identified histone deacetylase (HDAC) inhibitors as key epigenetic regulators in the neoplastic cells. Transcriptome analysis revealed that the neoplastic cells expressed all HDAC isoforms, except for HDAC4. Therefore, five HDAC inhibitors targeting different HDAC subtypes were selected for further studies. All GCTB cell lines were very sensitive to HDAC inhibition in both 2D and 3D in vitro models, and inductions in histone acetylation, as well as apoptosis, were observed. Thus, HDAC inhibition may represent a promising therapeutic strategy to eliminate the neoplastic cells from GCTB lesions, which remains the paramount objective for GCTB patients who require life-long treatment with denosumab.

Comparison of Distal Radius Autograft Technique with Iliac Crest Autograft Technique in Solitary Finger Enchondromas.

Objectives: The purpose of the study was to compare clinical and radiological outcomes of autografts obtained from the iliac crest (IC) and distal radius (DR) and to evaluate their superiority for surgical treatment of solitary finger enchondromas. Methods: Twenty-five patients for whom curettage and autografting were carried out for finger enchondroma were retrospectively analyzed. DR autograft was used in eight patients and IC autograft was used in 17 patients. Data on pre-operative total active motion (TAM), disabilities of the arm, shoulder, and hand (DASH) score, and pain visual analog scale (VAS) scores of the involved finger, duration of surgery, amount of bleeding during the operation, length of hospital stay, presence of complications related to anesthesia, and post-operative donor site morbidity were obtained. Pre-operative and post-operative 12th month radiographies were evaluated for pre-operative tumor volume, post-operative remnant volume, and Tordai radiologic evaluation grade. Results: No statistically significant difference could be identified between post-operative TAM (p=0.154), DASH (p=0.458), pain VAS scores (p=0.571), remnant volume (p=0.496), Tordai radiologic evaluation grade (p=0.522), duration of surgery (p=0.288), and amount of bleeding (p=0.114) between DR and IC groups. However, mean hospital stay duration was shorter for the DR group (p=0.0001). Recurrence was observed in one patient in the DR group and three patients in the IC group (p=0.996). Conclusion: The clinical and radiological outcomes of grafting from the DR and IC were similar in the treatment of hand enchondromas. However, grafting from the DR may result in shorter hospital stay compared to IC grafting.

Primary intraosseous solitary fibrous tumor: an extremely rare case report and brief review of the literature.

Solitary fibrous tumor (SFT), a rare mesenchymal neoplasm of fibroblastic origin, was initially discovered in the mediastinal pleura and then described in many extra-pleural sites.The reports of primary solitary fibrous tumor of bone are extremely rare and only a few cases have been previously mentioned in the literature, most of which in flat and short bones.Here we present the case of a 53-year-old female, who was referred to the emergency department of a peripheral hospital after an accidental fall. Imaging studies revealed an intertrochanteric fracture with an underlying intramedullary lytic lesion. A biopsy was performed and a diagnosis of Ewing sarcoma was initially suggested. She arrived at our hospital where we reevaluated the case. The biopsy was reviewed and a diagnosis of intraosseous SFT was proposed. She underwent en-block resection of the proximal right femur.Primary SFTs of the bone are, like in our case, easily misdiagnosed due to the low specificity of the imaging studies and the extreme rarity of the localization. An accurate diagnosis and early resection are very important and with careful long-term follow-up is essential, particularly in those who with malignant behavior, for the early detection of possible recurrence or metastasis.

Traumatic giant cell tumor of rib: A case report.

BACKGROUND: Giant cell tumor (GCT) of the anterior rib origin is extremely rare. We report the first case of trauma-induced GCT of the rib. CASE SUMMARY: A 22-year-old female developed a mass over the right anterior chest wall with pain 3 mo after a falling injury with blunt trauma of the right chest wall. Chest computed tomography (CT) showed a tumor originating from the right 6th rib with bony destruction, and a CT-guided needle biopsy revealed a GCT. We completely resected the tumor with chest wall and performed reconstruction. The pathological diagnosis was GCT of the bone. Twelve months after surgery, no signs of recurrence were observed. CONCLUSION: GCT of the rib after trauma has not been reported. Meticulous history-taking and image evaluation are essential for the differential diagnosis of unusual chest wall tumors.